U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry EPIMERIC
Molecular Formula C19H19ClN6O2
Molecular Weight 398.846
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DAROLUTAMIDE

SMILES

C[C@@H](CN1C=CC(=N1)C2=CC(Cl)=C(C=C2)C#N)NC(=O)C3=NNC(=C3)C(C)O

InChI

InChIKey=BLIJXOOIHRSQRB-PXYINDEMSA-N
InChI=1S/C19H19ClN6O2/c1-11(22-19(28)18-8-17(12(2)27)23-24-18)10-26-6-5-16(25-26)13-3-4-14(9-21)15(20)7-13/h3-8,11-12,27H,10H2,1-2H3,(H,22,28)(H,23,24)/t11-,12?/m0/s1

HIDE SMILES / InChI

Molecular Formula C19H19ClN6O2
Molecular Weight 398.846
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 1 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26137992 | https://www.ncbi.nlm.nih.gov/pubmed/26313416

ODM-201 (also known as BAY-1841788) is a non-steroidal antiandrogen, specifically, a full and high-affinity antagonist of the androgen receptor (AR), that is under development by Orion and Bayer HealthCare for the treatment of advanced, castration-resistant prostate cancer (CRPC). ODM-201 appears to negligibly cross the blood-brain-barrier. This is beneficial due to the reduced risk of seizures and other central side effects from off-target GABAA receptor inhibition that tends to occur in non-steroidal antiandrogens that are structurally similar to enzalutamide. Moreover, in accordance with its lack of central penetration, ODM-201 does not seem to increase testosterone levels in mice or humans, unlike other non-steroidal antiandrogens. Another advantage is that ODM-201 has been found to block the activity of all tested/well-known mutant ARs in prostate cancer, including the recently-identified clinically-relevant F876L mutation. ODM-201 has been studied in phase I and phase II clinical trials and has thus far been found to be effective and well-tolerated, with the most commonly reported side effects including fatigue, nausea, and diarrhea. No seizures have been observed.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
65.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.79 mg/L
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
52.82 μg × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
20 h
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ODM-201 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Disc. AE: Cardiac failure, Hypertension...
AEs leading to
discontinuation/dose reduction:
Cardiac failure (0.4%)
Hypertension (0.6%)
Diarrhea (0.5%)
Pneumonia (0.5%)
Fatigue (0.7%)
Hypertension (0.3%)
Nausea (0.3%)
Sources:
900 mg 2 times / day steady, oral
Highest studied dose
Dose: 900 mg, 2 times / day
Route: oral
Route: steady
Dose: 900 mg, 2 times / day
Sources:
unhealthy
AEs

AEs

AESignificanceDosePopulation
Hypertension 0.3%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Nausea 0.3%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Cardiac failure 0.4%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Diarrhea 0.5%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Pneumonia 0.5%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Hypertension 0.6%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
Fatigue 0.7%
Disc. AE
600 mg 2 times / day steady, oral
Recommended
Dose: 600 mg, 2 times / day
Route: oral
Route: steady
Dose: 600 mg, 2 times / day
Sources:
unhealthy, 74 years (range: 48–95 years)
Health Status: unhealthy
Age Group: 74 years (range: 48–95 years)
Sex: M
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 4.46 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >2 uM]
no [IC50 >2 uM]
no [IC50 >2 uM]
no [IC50 >300 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >50 uM]
no [IC50 >60 uM]
no
no
no
no
no
no
no
no
no
weak
weak (co-administration study)
Comment: decreased the mean exposure (AUC) and Cmax of midazolam by 29% and 32%, respectively; did not show any increase but a mean decrease of less than 20% in the mean exposure (AUC) and Cmax of non-conjugated or total dabigatran
Page: 71.0
yes [IC50 0.567 uM]
yes [IC50 1.33 uM]
yes (co-administration study)
Comment: showed a 5.2-fold increase in AUC and a 4.9-fold increase in Cmax of rosuvastatin
Page: 72.0
yes [IC50 16.4 uM]
yes [IC50 16.8 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
yes [IC50 2.57 uM]
yes [IC50 2.96 uM]
yes [IC50 32.3 uM]
yes [IC50 39.3 uM]
unlikely (co-administration study)
Comment: no change in the total and renal clearance of rosuvastatin by darolutamide
Page: 72.0
yes [IC50 9.5 uM]
yes [IC50 >10 uM]
yes [IC50 >10 uM]
yes [IC50 >10 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: significant reduction in darolutamide exposure (72% reduction in darolutamide AUC72) when it is concomitantly used with rifampin; Inhibition of CYP3A4 and P-gp by itraconazole increased darolutamide exposure (AUC72) by 1.7­ fold
Page: 72.0
yes
yes (co-administration study)
Comment: significant reduction in darolutamide exposure (72% reduction in darolutamide AUC72) when it is concomitantly used with rifampin; Inhibition of CYP3A4 and P-gp by itraconazole increased darolutamide exposure (AUC72) by 1.7­ fold
Page: 72.0
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
ODM-201: a new-generation androgen receptor inhibitor in castration-resistant prostate cancer.
2015
ODM-201 tablets complete phase I.
2015 Dec
Patents

Sample Use Guides

In the Phase II patients were treated orally with 200 mg/day, 400 mg/day or 1400 mg/day of ODM-201.
Route of Administration: Oral
Antagonism to wtAR was determined using AR-HEK293 cells treated with ODM-201 up to 1 uM. The cells were treated with test compounds and 0.45 nM testosterone in steroid-free assay medium. After 24 hours cells were lysed and luciferase activity was measured.
Substance Class Chemical
Created
by admin
on Mon Mar 31 23:42:41 GMT 2025
Edited
by admin
on Mon Mar 31 23:42:41 GMT 2025
Record UNII
X05U0N2RCO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DAROLUTAMIDE
INN   WHO-DD  
INN  
Official Name English
darolutamide [INN]
Preferred Name English
NUBEQA
Brand Name English
1H-PYRAZOLE-3-CARBOXAMIDE, N-((1S)-2-(3-(3-CHLORO-4-CYANOPHENYL)-1H-PYRAZOL-1-YL)-1-METHYLETHYL)-5-(1-HYDROXYETHYL)-
Systematic Name English
DAROLUTAMIDE [JAN]
Common Name English
N-((2S)-1-(3-(3-CHLORO-4-CYANOPHENYL)-1H-PYRAZOL- 1-YL)PROPAN-2-YL)-5-((1RS)-1-HYDROXYETHYL)-1H-PYRAZOLE- 3-CARBOXAMIDE
Systematic Name English
ODM-201
Code English
DAROLUTAMIDE [MI]
Common Name English
DAROLUTAMIDE [ORANGE BOOK]
Common Name English
BAY1841788
Code English
Darolutamide [WHO-DD]
Common Name English
DAROLUTAMIDE [USAN]
Common Name English
BAY-1841788
Code English
Classification Tree Code System Code
NCI_THESAURUS C146993
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
Code System Code Type Description
MERCK INDEX
m12159
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
DRUG BANK
DB12941
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
INN
10227
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
EVMPD
SUB185326
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
DRUG CENTRAL
5334
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
DAILYMED
X05U0N2RCO
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
CAS
1598419-57-8
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
NO STRUCTURE GIVEN
ChEMBL
CHEMBL3545294
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
SMS_ID
100000171715
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
USAN
EF-122
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
FDA UNII
X05U0N2RCO
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
RXCUI
2180325
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
NCI_THESAURUS
C104748
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
CAS
1297538-32-9
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
WIKIPEDIA
ODM-201
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
PUBCHEM
67171867
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
EPA CompTox
DTXSID101027953
Created by admin on Mon Mar 31 23:42:41 GMT 2025 , Edited by admin on Mon Mar 31 23:42:41 GMT 2025
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
ENANTIOMER -> ENANTIOMER
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
BINDING
Ki
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
URINE
METABOLITE -> PARENT
METABOLITE -> PARENT
MINOR
URINE
METABOLITE ACTIVE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC MULTIPLE ORAL ADMINISTRATION

blood-to-plasma ratio PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC